Towards an integrative picture of human sickness behavior

- A random-effects meta-analysis of human sickness behavior research was conducted.
- Three pro-inflammatory cytokines show significant associations with sickness behavior.
- IL-6 shows the strongest association with sickness behavior.
- TNF-α is understudied in this literature.
- High inter-study heterogeneity characterizes the literature.

Sickness behavior, a coordinated set of behavioral changes during infection and elicited by the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), is well studied in non-human animals. Over the last two decades, several papers have expanded this research to include humans. However, these studies use a variety of research designs, and typically focus on a single cytokine and only a few of the many behavioral changes constituting sickness behavior. Therefore, our understanding of human sickness behavior remains equivocal. To generate a more holistic, integrative picture of this phenomenon, a meta-analysis of the human sickness behavior literature was conducted. Full model results show that both IL-6 and IL-1β have significant relationships with sickness behavior, and the strength of these relationships is affected by a number of study parameters, such as type of immune stimulus and inclusion of controls. In addition to research design heterogeneity, other issues to address in future studies include an unequal focus on different cytokines and different sickness behaviors.